DESCRIPTION: The goal of this proposal is to establish the minimum concentration of fluoride needed to prevent enamel and root caries. The lack of knowledge about "the target concentration of fluoride required in the oral environment to optimize its potential for caries prevention" has inspired the NIDCR to issue a program announcement (PA-01-121) indicating a high priority status for this subject. After 60 years of community water fluoridation we still do not know how much F is required to prevent caries. This may be because no one has systematically performed in vitro studies that separate the significant factors under conditions that closely mimic those of the oral environment and then validated those findings in intraoral studies. This proposal details such a systematic study to identify the significant factors and their interactions as related to the efficacy of fluoride to prevent caries. A predictive model that takes into account the conditions of each person is to be developed from in vitro studies and then validated through intraoral studies. In the mouth, fluoride originates either from the saliva at a relatively low and fairly constant concentration (0.1 ppm;Carey et al., 1986) or from fluoride rinses, gels, and dentifrices, which is transient and can range in concentration up to 15,000 ppm. In Aim 1 the continuous flow model is used to optimize the amount of fluoride that is needed to prevent enamel caries when there is a steady, low concentration of fluoride at all times. Aim 2 is focused on determining the amount of fluoride on a time-weighted basis that is required to prevent enamel caries when the fluoride is provided as a bolus treatment twice daily. Recognizing that root dentin is a very different substrate than enamel, Aims 3 and 4 are focused on determining the therapeutic amounts of fluoride required to prevent root caries under conditions of constant exposure (Aim 3) and periodic high concentration fluoride exposures (Aim 4). Aim 5 will establish the amount of fluoride required to prevent caries when proteins or other permselective macromolecules are adsorbed on the surfaces of the enamel or root dentin. In Aim 6, the relationships between saliva composition, salivary flow and the amount of fluoride required to prevent caries established with the continuous flow model will be tested by use of an intraoral model. In this Aim 6 the effect of fluoride exposure on the prevention of caries will be determined. Together these studies should, for the first time, be able to demonstrate the minimum therapeutic levels of fluoride necessary to have a prophylactic effect. Additionally, the potential of this project to develop predictive models that can be used to indicate the required amount of F as a function of a specific environment is particularly significant because the profession will be able to tailor F regimes as appropriate. This is particularly important in the treatment of populations that are at higher risk.